Resting-state functional MRI shows altered default-mode network functional connectivity in Duchenne muscular dystrophy patients

Brain Imaging and Behavior, vol. 15, pp. 2297–2307

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder caused by absence of dystrophin protein. Dystrophin is expressed in muscle, but also in the brain. Difficulties with attention/inhibition, working memory and information processing are well described in DMD patients but their origin is poorly understood. The default mode network (DMN) is one of the networks involved in these processes. Therefore we aimed to assess DMN connectivity in DMD patients compared to matched controls, to better understand the cognitive profile in DMD. T1-weighted and resting state functional MRI scans were acquired from 33 DMD and 24 male age-matched controls at two clinical sites. Scans were analysed using FMRIB Software Library (FSL). Differences in the DMN were assessed using FSL RANDOMISE, with age as covariate and threshold-free cluster enhancement including multiple comparison correction. Post-hoc analyses were performed on the visual network, executive control network and fronto-parietal network with the same methods. In DMD patients, the level of connectivity was higher in areas within the control DMN (hyperconnectivity) and significant connectivity was found in areas outside the control DMN. No hypoconnectivity was found and no differences in the visual network, executive control network and fronto-parietal network. We showed differences both within and in areas outside the DMN in DMD. The specificity of our findings to the DMN can help provide a better understanding of the attention/inhibition, working memory and information processing difficulties in DMD.

Authors 8

1. Nathalie Doorenweerd corresponding Aachen C. J. Gorter Center for High Field MRI Department of Radiology, Leiden University Medical Center

   Leiden University · Leiden University Medical Center · Newcastle upon Tyne Hospitals NHS Foundation Trust · Newcastle University

   Affiliation as printed

   C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, C-03-Q, P.O. Box 9600, 2300, RC, Leiden, The Netherlands. n.doorenweerd@lumc.nl

   John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK. n.doorenweerd@lumc.nl

   John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK

2. Mischa de Rover Aachen Clinical Psychology Unit Institute of Psychology, Leiden University Department of Anesthesiology, Leiden University Medical Center

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Clinical Psychology Unit, Institute of Psychology, Leiden University, Leiden, The Netherlands

   Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands

3. Chiara Marini‐Bettolo

   Newcastle upon Tyne Hospitals NHS Foundation Trust · Newcastle University

   Affiliation as printed

   John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK

4. Kieren G. Hollingsworth

   Newcastle University

   Affiliation as printed

   Newcastle Magnetic Resonance Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK

5. Erik Harmen Niks Aachen Department of Neurology, Leiden University Medical Center (LUMC)

   Leiden University Medical Center

   Affiliation as printed

   Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands

6. Jos G.M. Hendriksen

   Maastricht University Medical Centre · Maastricht University · Kempenhaeghe

   Affiliation as printed

   Department of Neurological Learning Disabilities, Kempenhaeghe Epilepsy Center, Heeze, The Netherlands

   Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands

7. Hermien E. Kan Aachen C.J. Gorter Center for High Field MRI Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, C-03-Q, P.O. Box 9600, 2300, RC, Leiden, The Netherlands

8. Volker W. Straub

   Newcastle upon Tyne Hospitals NHS Foundation Trust · Newcastle University

   Affiliation as printed

   John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK